IN-VITRO EFFECT OF CETIRIZINE ON PGE(2) RELEASE BY RAT PERITONEAL-MACROPHAGES AND HUMAN MONOCYTES

Cetirizine was first described as a specific anti-H-1 molecule display ing potent antiallergic activity. It was later found that its pharmaco logical properties extended to cellular actions as on eosinophil recru itment at inflammatory sites in allergic patients. Monocytes and macro phages participate in allergic mechanisms, particularly through high a ffinity H-1 and H-2 membrane receptors and generation of pro- and anti -inflammatory agents; among them histamine-induced factors, IL-1 and p rostanoids are of importance. The aim of this work was to investigate the effect exerted by various concentrations of cetirizine (0.1-10 mu g/ml) applied in vitro to human monocytes and peritoneal rat macrophag es cultured for 24 h. Peritoneal macrophages were collected either fro m normal or experimentally inflamed rats. Human monocytes, isolated fr om peripheral blood, were studied either in a resting state or after s timulation by LPS from Escherichia coli (1 and 10 mu g/ml). Cetirizine (10 mu g/ml) significantly enhanced IL-1 release by human monocytes s timulated by a weak LPS concentration (1 mu g/ml) but could not modify the maximal increase of IL-1 release induced by 10 mu g/ml of LPS. It did not exert any effect on resting cells. Cetirizine (0.1-10 mu g/ml ) enhanced PGE(2) release by resting human monocytes. Concentrations o f 1 and 10 mu g/ml enhanced PGE(2) release by LPS-stimulated monocytes , and by healthy and inflamed rat macrophages. This effect was concent ration-dependent. Our findings point to an antiinflammatory action of cetirizine via PGE(2) release and histamine H-2 interactions. Cetirizi ne did not directly modify IL-1 generation by resting monocytes but th e IL-1 production observed after LPS stimulation could promote the mec hanisms by which PGE(2) is released.